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Synergistic Effects of 2-Deoxy-D-Glucose and Cinnamic Acid with Erlotinib on NSCLC Cell Line
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Background: In spite of all efforts, Non-small cell lung cancer (NSCLC) is a fatal solid tumor with a poor prognosis as of its high metastasis and resistance to present treatments. Tyrosine kinase inhibitors (TKI) such as erlotinib are efficient in treating NSCLC but the emergence of chemoresistance and adverse effects substantially limits their single use. Objective: in this study, the combination treatments of either 2-deoxy-D-glucose (2DG) or cinnamic acid (CINN) with erlotinib (ERL) were tested for their possible synergistic effect on the proliferation and migration capacity of NSCLC cells. Methods: In this study, NSCLC model cell line A549 was used to investigate the effects of single compounds and their combination on cell growth inhibition, clonogenic potential, and migration capacity. Next, the Combination index (CI) and the Dose-Reduction Index (DRI) were determined to determine the nature of the drug’s combination and to measure how many folds the dose could be lowered for each drug in a synergistic combination. Results: the combination treatment demonstrated more significant inhibition of viability of A549 cells compared to individual therapy. Our data show that CINN augments the sensitivity to erlotinib in all doses tested. The combination of 2DG or CINN with erlotinib also reduced the clonogenicity of NSCLC cells up to 67% and 85%, respectively, as compared to the erlotinib single treatment. Furthermore, CINN +ERL decreased the migratory ability of A549 cells by 3-fold and further induced much more apoptotic cell death phenotypes. Conclusion: in summary, co-administration of 2DG or cinnamic acid with erlotinib increases the inhibitory effects of erlotinib on NSCLC cell tumorigenicity and migration.

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Publication Date
Fri Feb 28 2025
Journal Name
Moroccan Journal Of Chemistry
Design, Synthesis, and Biological Evaluation of new sulfonamides derived from 2-Aminopyridine: Molecular docking, POM analysis, and identification of the pharmacophore sites
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New series of imidazole[1,2-a]pyridine-sulfonamides was designed and synthesized from 2-aminopyridine, which was reacted with p-bromo phenacyl bromide in the present of MgO to produce the corresponding imidazole[1,2-a]pyridine, which was then reacted with chlorosulfonic acid to produce 2-(4-bromophenyl)imidazole[1,2-a]pyridine-3-sulfonyl chloride [2]. Following that, treatment of (2) with different amines using the grand method to generate imidazole [1,2-a] pyridine sulfonamides. All the synthesized compounds have been characterized by FTIR, 1HNMR and 13CNMR and C.H.N analysis. The DFT, POM analysis and molecular docking were carried out on for all final compounds to investigate drug like attributes, and the results revealed showed that the

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Publication Date
Sun Dec 10 2017
Journal Name
Journal Of Pharmaceutical, Chemical And Biological Sciences
BRCA1 is Overexpressed in Breast Cancer Cell Lines and is Negatively Regulated by E2F6 in Normal but not Cancerous Breast Cells
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This study focused on the expression and regulation of BRCA1 in breast cancer cell lines compared to normal breast. BRCA1 transcript levels were assessed by real time quantitative polymerase chain reaction (RT-qPCR) in the cancer cell lines. Our data show overexpression of BRCA1 mRNA level in all the studied breast cancer cell lines: MCF-7, T47D, MDA-MB-231 and MDA-MB-468 along with Jurkat, leukemia T-lymphocyte, the positive control, relative to normal breast tissue. To investigate whether a positive or negative correlation exists between BRCA1 and the transcription factor E2F6, three different si-RNA specific for E2F6 were used to transfect the normal and cancerous breast cell lines. Interestingly, strong negative relationship was found b

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Publication Date
Wed Jan 01 2025
Journal Name
Advances In Animal And Veterinary Sciences
Exposure to Environmental Perfluorooctanoic Acid (PFOA) Induced Hepatocellular Apoptosis and Alteration in Serum Biomarkers in Diabetic Guinea Pigs
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Publication Date
Sat Jul 30 2016
Journal Name
Hepatology
Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice
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Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption. OCA markedly inhibits hepatic cholesterol 7α‐hydroxylase (Cyp7a1) and sterol 12α‐hydroxylase (Cyp8b1) partly through inducing small heterodimer partner, leading to reduced bile acid pool size and al

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Publication Date
Fri Jan 01 2016
Journal Name
Applied And Computational Mathematics
Memory Effects Due to Fractional Time Derivative and Integral Space in Diffusion Like Equation Via Haar Wavelets
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Publication Date
Sat Apr 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Proposal framework to activate the international accounting procedures for disasters and wars effects in the local environment
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natural and non-natural disasters, is an environmental challenges the society and the economy as well as a direct and indirect economic affect, and the units are part of the system overlapping among themselves and thus affected by external indicators, directly or indirectly, these direct effects appear in the destruction or damage inflicted by disasters in property , infrastructure , superstructure , accounting information systems and indirectly in the outcome of future business, comes research problem through access to accounting treatments issued by the Federal Office of financial supervision to address the damage caused by the disasters and prepare the missing financial accounts it turns out us that there is negligence of a nu

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Publication Date
Tue Mar 23 2021
Journal Name
International Journal Of Energy Research
Localized heating element distribution in composite metal foam‐phase change material: Fourier's law and creeping flow effects
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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preventive Effects of Different Doses of Pentoxyfilline Against CCl4-Induced Liver Toxicity in Rats
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The liver protective effects of pentoxifylline were studied through pre-treatment of rats with various intraperitoneal (IP) doses (25, 50 and 100mg/kg/day) 14 days before induction of liver toxicity by carbon tetrachloride (CCl4). The parameters of oxidative stress, malondialdehyde (MDA) and reduced glutathione (GSH) were measured in liver homogenate in addition to histopathological examinations.  Analysis of data revealed significant amelioration of oxidative stress in groups of animals pre-treated with different doses of pentoxifylline (PTX) compared to group of animals intoxicated by CCl4 as evidenced by lowering MDA contents and elevation of GSH levels in liver tissue homogenate but the levels still signifi

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Publication Date
Wed Jan 01 2020
Journal Name
Annals Of Tropical Medicine And Public Health
Cytopathic effects of activated parasporal inclusion proteins produced from Iraqi isolates of Bacillus thuringiensis
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Six isolates of Bacillus thuringiensis were isolated from Iraqi soil characterized as non- insecticidal and non- hemolytic parasporal inclusion proteins. Bacterial isolates were propagated on nutrient broth. Then, the parasporal inclusion proteins were extracted and processed with proteinase K and trypsin. The major protein segments produced of 64KDa were characterized and tested for cytocidal activity against human leukemic T- cells (CLL) (Chronic lymphoid leukemia). Results indicated that the treated parasporal proteins of four isolates (Bt2, Bt3, Bt4 and Bt6) showed strong cytotoxicity with no significant differences between normal lymphocytes and leukemic lymphocytes. Two isolates BtA1 and BtA5 show discriminative cytotoxicity between n

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Publication Date
Sat Dec 24 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Possible protective effects of two different doses of cyanocobalamin against methotrexate nephrotoxicity in rats
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Abstract

   Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rat

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